The phosphorylation of protein tyrosine residues is closely linked to cell growth and transformation. Methodological obstacles have been overcome which allow the measurement of protein tyrosine kinase and protein phosphotyrosine phosphatase in cells. The assay has been used to quantify protein tyrosine kinase activity in normal and malignant cells. Protein tyrosine kinase activity was found to be associated with increased cell division, and/or activated in the transformed state but not in the normal state by particlar growth factors. These features may be important in regulating protein tyrosine phosphorylation in vivo. Assay of protein phosphotyrosine phosphatase activity (PTPase) has been carried out in normal and cancerous cells using radioactive phosphotyrosine glutamine synthetase. Characteristics of the PTPase activity in Ehrlich Ascities Tumor (EAT) cells are: the activity is predominately cytosolic and dilution-dependent with maximal activities about 5 nmol/min/mg. Heat stable nondialyzable inhibitors of the PTPase were found and characterized in boiled cell extracts which could act as regulatory molecules. The substrate was used to characterize the protein phosphotyrosine phosphatase activity of calcinerurin: Antiboides which recognize tyrosine phosphate have been successfully used to develop immunological detection methods for phosphotyrosine containing proteins.